Bisphenol S and high-fat diet drive structural and inflammatory remodeling of the colon in C57Bl/6 male mice.

Bisphenol S (BPS) is an emerging environmental contaminant with endocrine-disrupting properties capable of triggering early gastrointestinal alterations linked to intestinal remodeling. This study investigated the effects of BPS and a high-fat diet (HFD) on colon remodeling in male mice. Forty animals were divided into four groups: standard chow (SC), SC+BPS (SCB), HFD, and HFD+BPS (HFB). After 12 weeks, biometric parameters and colon morphology were analyzed. Both BPS and HFD induced weight gain, adiposity, and reductions in colon length, crypt depth, and mucus-positive area. Altered tight junction protein expression (decreased Occludin, and increased Claudin-2) suggested impaired epithelial barrier integrity. Higher TLR-4 expression and serotonin-secreting cells supported the presence of local inflammation. The combination of BPS and HFD did not potentiate these effects. Chronic exposure to BPS, even at low doses, promotes adverse colon remodeling comparable to that induced by HFD, and might compromise barrier integrity, and enhance local inflammation. These findings raise concerns about BPS safety and highlight the need for stricter regulation of bisphenol analogues in food packaging.